Regular intake of polyphenol-rich food has been associated with a wide variety of beneficial health effects, including the prevention of cardiovascular diseases. However, the parent flavonoids have mostly low bioavailability and, hence, their metabolites have been hypothesized to be bioactive. One of these metabolites, 3-hydroxyphenylacetic acid (3-HPAA), formed by the gut microbiota, was previously reported to exert vasorelaxant effects ex vivo. The aim of this study was to shed more light on this effect in vivo, and to elucidate the mechanism of action. 3-HPAA gave rise to a dose-dependent decrease in arterial blood pressure when administered i.v. both as a bolus and infusion to spontaneously hypertensive rats. In contrast, no significant changes in heart rate were observed. In ex vivo experiments, where porcine hearts from a slaughterhouse were used to decrease the need for laboratory animals, 3-HPAA relaxed precontracted porcine coronary artery segments via a mechanism partially dependent on endothelium integrity. This relaxation was significantly impaired after endothelial nitric oxide synthase inhibition. In contrast, the blockade of SKCa or IKCa channels, or muscarinic receptors, did not affect 3-HPAA relaxation. Similarly, no effects of 3-HPAA on cyclooxygenase nor L-type calcium channels were observed. Thus, 3-HPAA decreases blood pressure in vivo via vessel relaxation, and this mechanism might be based on the release of nitric oxide by the endothelial layer.

中文翻译：

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3-羟基苯乙酸：一种降血压的类黄酮代谢物

经常摄入富含多酚的食物与多种有益的健康影响有关，包括预防心血管疾病。然而，母体黄酮类化合物大多具有低生物利用度，因此，它们的代谢物被假设为具有生物活性。其中一种代谢物 3-羟基苯乙酸 (3-HPAA) 由肠道微生物群形成，此前曾有报道称其在体外发挥血管舒张作用。本研究的目的是进一步阐明这种体内效应，并阐明作用机制。当以推注和输注方式向自发性高血压大鼠静脉内给药时，3-HPAA 引起动脉血压的剂量依赖性降低。相反，没有观察到心率的显着变化。在离体实验中，在使用来自屠宰场的猪心脏来减少对实验动物的需求时，3-HPAA 通过部分依赖于内皮完整性的机制放松了预收缩的猪冠状动脉节段。内皮一氧化氮合酶抑制后，这种松弛显着受损。相比之下，SKCa 或 IKCa 通道或毒蕈碱受体的阻断不影响 3-HPAA 松弛。同样，没有观察到 3-HPAA 对环氧合酶和 L 型钙通道的影响。因此，3-HPAA 通过血管舒张降低体内血压，这种机制可能是基于内皮层释放一氧化氮。内皮一氧化氮合酶抑制后，这种松弛显着受损。相比之下，SKCa 或 IKCa 通道或毒蕈碱受体的阻断不影响 3-HPAA 松弛。同样，没有观察到 3-HPAA 对环氧合酶和 L 型钙通道的影响。因此，3-HPAA 通过血管舒张降低体内血压，这种机制可能是基于内皮层释放一氧化氮。内皮一氧化氮合酶抑制后，这种松弛显着受损。相比之下，SKCa 或 IKCa 通道或毒蕈碱受体的阻断不影响 3-HPAA 松弛。同样，没有观察到 3-HPAA 对环氧合酶和 L 型钙通道的影响。因此，3-HPAA 通过血管舒张降低体内血压，这种机制可能是基于内皮层释放一氧化氮。